1-Bromo-2-methoxy-3-nitro-benzene

White to off-white powder

To a mixture of the compound represented by the structural formula (O-1) (19.6 g, 90.0 mmol) and potassium carbonate (24.9 g, 180 mmol) in acetone (400 mL), iodomethane (25.6 g, 180 mmol) was added. Stepi[00172j 2-Bromo-6-nitrophenol (5.0 g, 22.9 mmol) was dissolved in DMF (3 mL), potassium carbonate (4.75 g, 34.4 mmol) was added and the reaction was stirred for 30 minutes. Next iodomethane (2.15 mL, 34.4 mmol) was added and the reaction was stirred overnight. The crude reaction was filtered, diluted with ethyl acetate and washed with brine (twice) and water (twice). The organic layer was dried over sodium sulfate, filtered and concentrated to provide Int9 (5.12 g, 96percent). LC retention time 0.92 [J].A mixture of 2-Bromo-6-nitro-phenol (43.6 g, 0.2 mol), Kl-Bromo-2-methoxy-3-nitro-benzene A mixture of 2-Bromo-6-nitro-phenol (43.6 g, 0.2mol), KStep 2 1-Bromo-2-methoxy-3-nitro-benzene; 2-Bromo-6-nitro-phenol 1b (46.55 g, 0.214 mol) was dissolved in 500 mL of acetone followed by addition of potassium carbonate (35.36 g, 0.256 mol) and iodomethane (20.1 mL, 0.32 mol). The reaction mixture was heated to reflux at 70 °C for 40 hours. The reaction was monitored by TLC until the disappearance of the starting materials. The reaction mixture was concentrated under reduced pressure and diluted with 1300 mL of ethyl acetate and 500 mL of water. The aqueous layer was extracted with ethyl acetate (300 mL.x.2). The combined organic extracts were washed with 4 N hydrochloric acid and saturated aqueous sodium bicarbonate and then dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 1-bromo-2-methoxy-3-nitro-benzene 1c (44.59 g, yield 90.0percent) as a brown solid. MS m/z (ESI): 234 [M+1]Step 2 1-Bromo-2-methoxy-3-nitro-benzene; 2-Bromo-6-nitro-phenol 1b (46.55 g, 0.214 mol) was dissolved in 500 mL of acetone followed by addition of potassium carbonate (35.36 g, 0.26 mol) and iodo- methane (20.1 mL, 0.32 mol). The reaction mixture was heated to reflux at 70°C for 40 hours. The reaction mixture was concentrated under reduced pressure and diluted with 1300 mL of ethyl acetate and 500 mL of water. The aqueous layer was extracted with ethyl acetate (300 mLx2). The combined organic extracts were washed with 4 M hydrochloric acid and saturated sodium bicarbonate solution and then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 1-bromo-2-methoxy-3-nitro-benzene 1c (44.59 g, yield 90.0percent) as a brown solid. MS m/z (ESI): 234 [M+1]2-bromo-6-nitrophenol 1b (46.55g, 0.214mol) was dissolved in 500mL acetone. To this was added potassium carbonate (35.36g, 0.26mol) and iodomethane (20.1mL, 0.32mol) then the solution was heated at reflux 70°C for 40 hours. The reaction solution was concentrated under reduced pressure. Added 1300mL ethyl acetate and 500mL water. The aqueous phase was extracted with ethyl acetate (300mL × 2). The combined organic phases were washed with 4M hydrochloric acid and saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The result was purified by column chromatography on silica gel to give 1-bromo-2-methoxy-3-nitrobenzene 1c (44.59g, brown solid). Yield: 90.0percent.Preparation 12 To a solution of 2-bromo-6-nitrophenol (5 g, 22.94 mmol) in DMF (18 ml) was added potassium carbonate (9.51 g, 68.8 mmol) and the resulting mixture was stirred for 15 min, then iodomethane (2.87 ml, 45.9 mmol) was added. The resulting mixture was stirred at rt overnight. HPLC and LCMS indicated complete conversion to product. Cold water added (75 mL), stir/sonicate, solid was collected by filtration. This material was then dissolved in EtOAc (150 mL). This solution was washed lx 10percent LiCl, lx brine. dried over sodium sulfate, then filtered and concentrated. Loaded onto a 120g silica gel cartridge, then purified by flash chromatography eluting with 0-50percent EtOAc in hexanes. Fractions containing the product were concentrated to afford a pale yellow solid as the product l-bromo-2-methoxy-3 -nitrobenzene (4.997 g, 20.46 mmol, 89percent yield). LCMS ave very weak MH+.To a solution of 2-bromo-6-nitrophenol (5 g, 22.94 mmol) in DMF (18 ml) was added potassium carbonate (9.51 g, 68.8 mmol) and the resulting mixture was stirred for 15 min and then iodomethane (2.87 ml, 45.9 mmol). The resulting mixture was stirred overnight at rt. HPLC and LCMS instructions were fully converted to product. Add cold water (75 mL), perform agitation / sonic processing, and collect solids by filtration. The material was then dissolved in EtOAc (150 mL). The solution was washed with 10percent LiCl, washed 1x with brine, dried over sodium sulfate, filtered and concentrated. Was loaded onto a 120 g silica gel cartridge and then purified by flash chromatography eluting with 0-50percent EtOAc in hexanes. Concentrate the fractions containing the product to afford the product as a pale yellow solid 1-bromo-2-methoxy-3-nitrobenzene (4.997 g, 20.46 mmol, 89percent yield).To a mixture of 2-bromo-6-nitrophenol (5.0 g, 22.9 mmol) and potassium carbonate (6.3 g, 45.8 mmol) in acetone (100 mL) was added iodomethane (2.85 mL, 45.8 mmol) under stirring and the mixture was then heated to reflux overnight. The mixture was cooled to room temperature, filtered through Celite, the filter cake washed with ethyl acetate, and the filtrate concentrated under reduced pressure. The residue was taken up in ethyl acetate, washed 3x with IN NaOH, once with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was recrystallized twice from 2-propanol / water to give 4.45 g (83.6percent) of the title compound as beige, very fine needles.MS (ESI: 232 / 234 (M+HTo a mixture of K(v) To a stirred solution of 1-bromo-2-chloro-3-nitrobenzene (24.5 g, 0.10 mol) in methanol (250 ml.) in a 1 L autoclave was added sodium methoxide (8.43 g, 0.16 mol). The autoclave was then sealed and heated at 100°C for 3 h. Upon being allowed to cool to room temperature the majority of the solvent was removed under vacuum. Water and ethyl acetate were then added, the two layers were separated, and the aqueous layer was further extracted with ethyl acetate. The combined organic fractions were washed with 1 M aqueous sodium hydroxide (3A mixture of the compound from Example 2a) (10.8 g; 0.0495 mol.), methyl iodide (3.4 mL; 0.00545 mol.) and potassium carbonate (8.2 g; 0.0592 mol.) in acetone (250 mL) was stirred and heated under reflux for 24 h. [0392] The mixture was evaporated and the residue triturated with water to afford the title compound (8.7 g; 76percent). mp 55-56° C. 1H NMR (300 MHz, CDCl3 δ 7.81-7.74 (m, 2H), 7.13 (t, J=8.1 Hz, 1H), 4.02 (s, 3H); Anal. (C7H6NO3Br) calcd: C, 36.24; H, 2.61; N, 6.04. found: C, 36.30; H, 2.59; N, 5.73.

Molecular Weight:232.03
XLogP3:2.4
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:230.95311
Monoisotopic Mass:230.95311
Topological Polar Surface Area:55
Heavy Atom Count:12
Complexity:171
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes